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At least 19 recordsLinked to original sources
PubMed2000

Lateralization of temporal lobe epilepsy (TLE) and discrimination of TLE from extra-TLE using pattern analysis of magnetic resonance spectroscopic and volumetric data.

PURPOSE: To examine whether or not pattern analysis of magnetic resonance volumetric (MRVol) and proton magnetic resonance spectroscopic imaging (1H-MRSI) data would enable (a) the accurate lateralization of temporal lobe epilepsy (TLE) and (b) the discrimination of TLE from extratemporal epilepsy (E-TLE). METHODS: For lateralization analysis, we used data from 150 nonforeign tissue lesional TLE patients [88 left-sided (L-TLE), 46 right-sided (R-TLE), and 16 bilateral (Bi-TLE)]. For the discrimination of TLE from E-TLE, we used data from 174 patients (145 with unilateral TLE, 14 with unilateral E-TLE, and 15 with widespread epileptogenic zones involving both the TL and extra-TL regions-multilobar epilepsy). A series of "leave-one-out" cross-validated linear discriminant analyses were performed using the MRVol and 1H-MRSI data sets to lateralize TLE and discriminate it from E-TLE. RESULTS: Lateralization: The leave-one-out linear discriminant analyses were able to correctly lateralize (with a posterior probability >0.50) 120 (90%) of the 134 L-TLE and R-TLE patients. Imposing higher posterior probability (>0.95) increased accuracy of lateralization to 98%, with only two discordant cases who underwent surgery on the side of electroencephalogram, and both had bad outcome. Discrimination: the leave-one-out linear discriminant analyses were able to correctly classify (with a posterior probability >0.50) 142 (89%) of the 159 TLE and E-TLE patients. Accuracy increased slightly as higher posterior probability cutoffs were imposed, with fewer patients being classified. CONCLUSIONS: Pattern analysis of 1H-MRSI and MRVol data can accurately lateralize TLE. Discriminating TLE from E-TLE was less accurate, probably due to the presence of temporal lobe damage in some patients with E-TLE reflecting dual pathology.

Amygdala↗
PubMed2006

Interictal depression, anxiety, personality traits, and psychological dissociation in patients with temporal lobe epilepsy (TLE) and extra-TLE.

PURPOSE: This study was performed to investigate the relation between symptoms of interictal depression, anxiety, personality traits, and psychological dissociation with the localization and lateralization of the epileptogenic zone in patients with partial epilepsy. METHODS: All patients were diagnosed according to the localization-related concept of the 1989 International League Against Epilepsy (ILAE) Classification of Epilepsies and Epileptic Syndromes, and the localization and lateralization of the epileptogenic zone was established by using the clinical criteria for noninvasive presurgical evaluation. This resulted in 67 patients with temporal lobe epilepsy (TLE) and 64 patients with extra-TLE. All patients were assessed on the various aspects of psychopathology by using a comprehensive battery of standardized diagnostic instruments. RESULTS: We did not find the hypothesized excess of psychiatric symptoms in patients with (mesial) TLE in comparison with patients with extra-TLE. We also found no differences between patients with the lateralization of epilepsy in the left versus the right hemisphere. CONCLUSIONS: TLE per se cannot be considered a risk factor in developing more or more severe symptoms of psychopathology in patients with partial epilepsy. Concomitant factors, such as the duration of epilepsy, seizure frequency, and frontal lobe dysfunction may play an additional role. Our findings support the hypothesis of a multifactorial explanation for the psychiatric symptoms in patients with epilepsy.

Adult↗
PubMed1994

Effects of GABAA receptors activation on brain glucose metabolism in normal subjects and temporal lobe epilepsy (TLE) patients. A positron emission tomography (PET) study. Part II: The focal hypometabolism is reactive to GABAA agonist administration in TLE.

Positron emission tomography (PET) using [18F]fluorodeoxyglucose (FDG) was used to study the metabolic response of focal hypometabolism to the administration of a specific GABAA agonist (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), THIP, in six temporal lobe epilepsy (TLE) patients. After THIP injection, the increase of glucose metabolism in the hypometabolic focus was larger than the mean increase reported in the whole brain (Part I; Epilepsy Res., 19 (1994) 45-54). Within the hypometabolic focus, this increase was significantly higher in regions with the lowest basal metabolic level. This metabolic response in the hypometabolic focus, observed in the absence of any epileptic discharge during FDG accumulation and PET data acquisition, suggests that GABAA receptors are up-regulated or, at least, preserved in TLE.

Adult↗
PubMed2006

Voxel-based optimized morphometry (VBM) of gray and white matter in temporal lobe epilepsy (TLE) with and without mesial temporal sclerosis.

PURPOSE: In temporal lobe epilepsy (TLE) with evidence of hippocampal sclerosis (TLE-MTS) volumetric gray (GM) and white (WM) matter abnormalities are not restricted to the hippocampus but also are found in extrahippocampal structures. Less is known about extrahippocampal volumetric abnormalities in TLE without hippocampal sclerosis (TLE-no). In this study, we used optimized voxel-based morphometry (VBM) with and without modulation with the following aims: (a) to identify WM and GM abnormalities beyond the hippocampus in TLE-MTS and TLE-no; and (b) to determine whether extratemporal WM and GM abnormalities differ between TLE-MTS and TLE-no. METHODS: Optimized VBM of GM and WM with and without modulation was performed in 26 TLE-MTS (mean age, 35.6 +/- 9.7 years), 17 TLE-no (mean age, 35.6 +/- 11.1 years), and 30 healthy controls (mean age, 30.3 +/- 11.1 years). RESULTS: In TLE-MTS, GM/WM volume and concentration reductions were found in the ipsilateral limbic system, ipsi- and contralateral neocortical regions, thalamus, cerebellum, internal capsule, and brainstem when compared with controls. In contrast, no differences of GM/WM volumes/concentrations were found between TLE-no and controls or between TLE-no and TLE-MTS. CONCLUSIONS: In TLE-MTS, optimized VBM showed extensive GM and WM volume reductions in the ipsilateral hippocampus and in ipsi- and contralateral extrahippocampal regions. In contrast, no GM/WM volume or concentration reductions were found in TLE-no. This further supports the hypothesis that TLE-no is a distinct clinicopathologic entity from TLE-MTS and probably heterogeneous in itself.

Adult↗
PubMed1995

TLE expression correlates with mouse embryonic segmentation, neurogenesis, and epithelial determination.

The TLE proteins are the mammalian homologues of Groucho, a member of the Drosophila Notch signaling pathway. Notch signaling controls the differentiation of a variety of tissues in invertebrates and vertebrates. We are investigating the role of the TLE genes during mammalian development. We show that TLE 1 and TLE 3 are expressed during a number of cell-determination events, including embryonic segmentation, central and peripheral neurogenesis, and epithelial differentiation. This expression pattern is in agreement with the involvement of Groucho in similar fate choices in Drosophila and suggests that Groucho and TLE proteins perform similar developmental roles. Our results also show that TLE genes are co-expressed during a variety of cell-fate choices with several vertebrate homologues of genes implicated in the Drosophila Notch cascade, suggesting a role for the TLE proteins in mammalian Notch signaling.

Animals↗
PubMed2001

Disturbed benzodiazepine receptor function at the onset of temporal lobe epilepsy--lomanzenil-binding in de-novo TLE.

PURPOSE: Epileptogenic foci exhibit disturbed function at the level of the benzodiazepine receptor. The aim of our study was to investigate the incidence of focal reductions of temporal benzodiazepine receptor binding (BRB) as assessed by scintigraphy with 123I-iomazenil in patients with denovo temporal lobe epilepsy (TLE). METHODS: Forty adult patients (age: 34+/-12 years) with cryptogenic denovo TLE underwent scintigraphy with 123I-iomazenil. In all patients, symptomatic epilepsy was excluded by clinical investigation and MRI. The median duration of TLE was seven months, and the patients had a median of three documented seizures in their history of disease. BRB was quantified in four temporal regions covering the whole temporal lobe. Temporal asymmetry values (ASY) were compared with data determined in 13 age-matched controls yielding Z-scores for global and regional temporal BRB. RESULTS: A significant reduction of temporal BRB was found in 19 of the 40 patients (48 %), mainly in mesial temporal regions; temporal BRB asymmetries were also found in patients with a short history of seizures and low seizure frequency (< or = 1 year; n = 32, 13/32 (41 %)). Only in the entire cohort did the magnitude of temporal reduction of BRB correlate with the duration of TLE as well as with the number of previous partial seizures (r = 0.40 and r = 0.36; p < 0.03, respectively). CONCLUSIONS: Foci of decreased BRB can already be detected at the onset of TLE; their magnitude is related to ongoing epileptic activity.

Adolescent↗
PubMed1998

Combinatorial expression patterns of individual TLE proteins during cell determination and differentiation suggest non-redundant functions for mammalian homologs of Drosophila Groucho.

The Drosophila protein Groucho is involved in the regulation of cell-determination events during insect neurogenesis and segmentation. A group of mammalian proteins, referred to as transducin-like Enhancer of split (TLE) 1 through 4, share with Groucho identical structures and molecular properties. The aim was to determine whether individual TLE proteins participate in the regulation of cell determination in mammals like their Drosophila counterpart. It is here reported that TLE family members are expressed in combinatorial ways during the in vitro differentiation of mouse P19 embryonic carcinoma cells (a model for neural determination) and rat CFK2 cells (a model for chondrocytic determination). TLE1 is up-regulated and TLE2 and TLE4 are down-regulated to different extents during early stages of differentiation. In contrast, later stages correlate with up-regulation of TLE2 and TLE4, and decreased expression of TLE1. Individual TLE proteins are also expressed in combinatorial as well as complementary patterns during the development of the cerebral cortex and spinal cord of mouse embryos. In particular, TLE1 is robustly expressed in both neural progenitor cells and postmitotic neurons of the outer layers of the cortical plate, whereas TLE4 expression marks preferentially postmitotic neurons of the inner layers. Taken together, these results strongly suggest non-redundant roles for individual TLE proteins during both cell-determination and cell-differentiation events.

Animals↗
PubMed1996

Epithelial expression and chromosomal location of human TLE genes: implications for notch signaling and neoplasia.

The TLE genes are the human homologues of Drosophila groucho, a member of the Notch signaling pathway. This pathway controls a number of different cell-fate choices in invertebrates and vertebrates. We are interested in investigating the functions of the TLE gene family during epithelial determination and carcinogenesis. We show that expression of individual TLE genes correlates with immature epithelial cells that are progressing toward their terminally differentiated state, suggesting a role during epithelial differentiation. In both normal tissues and conditions resulting from incorrect or incomplete maturation events, such as metaplastic and neoplastic transformations, TLE expression is elevated and coincides with Notch expression, implicating these molecules in the maintenance of the undifferentiated state in epithelial cells. We also show that TLE1 and TLE2 are organized in a tandem array at chromosomal location 19p13.3, while TLE3 maps to 15q22.

Animals↗
PubMed1995

Comparison of tetracaine-adrenaline-cocaine (TAC) with topical lidocaine-epinephrine (TLE): efficacy and cost.

Topical anesthesia in the form of TAC (tetracaine, adrenaline, cocaine) solution has been used for wound repair. This pilot study was designed to determine if the topical anesthesia achieved using a mixture of lidocaine (5%) and epinephrine (1:2000) (TLE) is equivalent to the topical anesthesia obtained using a solution of tetracaine (0.5%), epinephrine (1: 2000), and cocaine (10.4%) (TAC). A prospective, randomized, double-blind trial was carried out from May 1992 to August 1992 at a community-based teaching hospital Emergency Department (ED) that receives 50,000 annual visits. Patients with facial or scalp lacerations suitable for topical anesthesia presenting to the ED were included when study physicians were in attendance. Exclusion criteria included the presence of a sensory altering substance (eg, ethanol), age younger than two years, hypertension, pregnancy, allergy to any of the study's pharmacological agents, wounds greater than six hours old, grossly contaminated wounds, and wounds longer than six centimeters. Either a TAC or TLE solution was applied to lacerations before suturing. The laceration was repaired and the patient or physician evaluated the degree of pain from the procedure by using a standardized visual pain scale. A total of 35 patients were studied. Seventeen patients were in the TLE group; 18 in the TAC group. The mean ages were compared and found to be similar (P = .40) between the two test groups. The pain scale values, the diameter of tissue blanch around laceration (halo size), and the time to laceration repair from the onset of application of anesthetic were compared and no difference was shown between the TAC and TLE groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2001

Pf1, a novel PHD zinc finger protein that links the TLE corepressor to the mSin3A-histone deacetylase complex.

The mSin3A-histone deacetylase corepressor is a multiprotein complex that is recruited by DNA binding transcriptional repressors. Sin3 has four paired amphipathic alpha helices (PAH1 to -4) that are protein-protein interaction motifs and is the scaffold upon which the complex assembles. We identified a novel mSin3A-interacting protein that has two plant homeodomain (PHD) zinc fingers we term Pf1, for PHD factor one. Pf1 associates with mSin3A in vivo and recruits the mSin3A complex to repress transcription when fused to the DNA binding domain of Gal4. Pf1 interacts with Sin3 through two independent Sin3 interaction domains (SIDs), Pf1SID1 and Pf1SID2. Pf1SID1 binds PAH2, while Pf1SID2 binds PAH1. Pf1SID1 has sequence and structural similarity to the well-characterized 13-amino-acid SID of the Mad bHLHZip repressor. Pf1SID2 does not have sequence similarity with either Mad SID or Pf1SID1 and therefore represents a novel Sin3 binding domain. Mutations in a minimal fragment of Pf1 that encompasses Pf1SID1 inhibited mSin3A binding yet only slightly impaired repression when targeted to DNA, implying that Pf1 might interact with other corepressors. We show that Pf1 interacts with a mammalian homolog of the Drosophila Groucho corepressor, transducin-like enhancer (TLE). Pf1 binds TLE in an mSin3A-independent manner and recruits functional TLE complexes to repress transcription. These findings suggest that Pf1 may serve to bridge two global transcription networks, mSin3A and TLE.

Amino Acid Sequence↗
PubMed1999

Groucho/transducin-like enhancer of split (TLE) family members interact with the yeast transcriptional co-repressor SSN6 and mammalian SSN6-related proteins: implications for evolutionary conservation of transcription repression mechanisms.

The yeast proteins TUP1 and SSN6 form a transcription repressor complex that is recruited to different promoters via pathway-specific DNA-binding proteins and regulates the expression of a variety of genes. TUP1 is functionally related to invertebrate and vertebrate transcriptional repressors of the Groucho/transducin-like Enhancer of split (TLE) family. The aim was to examine whether similar mechanisms underlie the transcription repression functions of TUP1 and Groucho/TLEs by determining whether TLE family members can interact with yeast SSN6 and mammalian SSN6-like proteins. It is shown in the present work that SSN6 binds to TLE1 and mediates transcriptional repression when expressed in mammalian cells. Moreover, TLE1 and TLE2 interact with two mammalian proteins related to SSN6, designated as the products of the ubiquitously transcribed tetratricopeptide-repeat genes on the Y (or X) chromosomes (UTY/X). These findings suggest that mammalian TLE and UTY/X proteins may mediate repression mechanisms similar to those performed by TUP1-SSN6 in yeast.

Basic Helix-Loop-Helix Proteins↗
PubMed2005

Factors affecting spiking related to sleep and wake states in temporal lobe epilepsy (TLE).

The aim of the study was to investigate the influence of different clinical factors on spiking during sleep and wakefulness in temporal lobe epilepsy. The study included 38 temporal lobe epilepsy (TLE) patients who underwent long-term electroencephalography (EEG) monitoring. In addition to traditional sleep scoring, waking was subdivided into eyes opened (WEO) and eyes closed (WEC) states. The following spike measures were investigated: spiking rates for each state, mean spike rate, spiking stability across wake and sleep states and relative spike density for each state. These measures were investigated according to clinical variables, such as age, age at epilepsy onset, duration of epilepsy, seizure frequency, the presence of secondarily generalised tonic-clonic (SGTC) seizures and the data on epileptogenic lesions based on MRI. Spiking rates during most states and spiking stability showed a significant positive correlation with epilepsy duration. Relative spike density during sleep stage NREM3,4 significantly increased with age at epilepsy onset. Relative spike density during WEC was significantly higher in the presence of hippocampal sclerosis (HS). Spiking rate during REM was significantly higher if a patient had SGTC seizures. Our data provide evidence that different aspects of spiking are associated with different aspects of TLE. We suggest that spike behaviour analysis offer new aspects both for diagnosis and research.

Adult↗
PubMed2001

Sequences of the NPS-1 and TLE-1 beta-lactamase genes.

The NPS-1 and TLE-1 beta-lactamase genes were cloned and sequenced. NPS-1 differed from LCR-1 beta-lactamase in 8 of 260 amino acids. TLE-1 differed from TEM-1 by a single Asp(115)-->Gly substitution and has been renamed TEM-90.

Amino Acid Sequence↗
PubMed2006

Groucho/transducin-like Enhancer-of-split (TLE)-dependent and -independent transcriptional regulation by Runx3.

Regulation of gene expression by tissue-specific transcription factors involves both turning on and turning off transcription of target genes. Runx3, a runt-domain transcription factor, regulates cell-intrinsic functions by activating and repressing gene expression in sensory neurons, dendritic cells (DC), and T cells. To investigate the mechanism of Runx3-mediated repression in an in vivo context, we generated mice expressing a mutant Runx3 lacking the C-terminal VWRPY, a motif required for Runx3 interaction with the corepressor Groucho/transducin-like Enhancer-of-split (TLE). In contrast with Runx3(-/-) mice, which displayed ataxia due to the death of dorsal root ganglia TrkC neurons, Runx3(VWRPY-/-) mice were not ataxic and had intact dorsal root ganglia neurons, indicating that ability of Runx3 to tether Groucho/TLE is not essential for neurogenesis. In the DC compartment, the mutant protein Runx3(VWRPY-) promoted normally developed skin Langerhans cells but failed to restrain DC spontaneous maturation, indicating that this latter process involves Runx3-mediated repression through recruitment of Groucho/TLE. Moreover, in CD8(+) thymocytes, Runx3(VWRPY-) up-regulated alphaE/CD103-like WT Runx3, whereas unlike wild type, it failed to repress alphaE/CD103 in CD8(+) splenocytes. Thus, in CD8-lineage T cells, Runx3 regulates alphaE/CD103 in opposing regulatory modes and recruits Groucho/TLE to facilitate the transition from activation to repression. Runx3(VWRPY-) also failed to mediate the epigenetic silencing of CD4 gene in CD8(+) T cells, but normally regulated other pan-CD8(+) T cell genes. These data provide evidence for the requirement of Groucho/TLE for Runx3-mediated epigenetic silencing of CD4 and pertain to the mechanism through which other Runx3-regulated genes are epigenetically silenced.

Amino Acid Sequence↗
PubMed1984

Effects of carbamazepine on interictal psychopathology in TLE with ictal fear.

Significant interictal psychopathology was manifested by a patient with temporal lobe epilepsy (TLE) who experienced an aura of intense fear. She was found to be taking a subtherapeutic dosage of carbamazepine; induction of therapeutic blood levels of carbamazepine resulted in improvement in the interictal EEG, decreased duration and intensity of affect during the epileptic attacks, and a normalization of behavioral and emotional functioning during the interictal period.

Adolescent↗
PubMed1998

TLE, the human homolog of groucho, interacts with AML1 and acts as a repressor of AML1-induced transactivation.

The AML1 gene encodes DNA-binding proteins that contain the Runt domain and is found at the breakpoints of some translocations associated with leukemias. It has been reported that AML1 plays pivotal roles in myeloid differentiation, probably through the transcriptional regulation of various hematopoietic genes. Here we demonstrate the physical and the functional interaction between AML1 and TLE1 (transducin-like Enhancer of split) human homolog of Groucho that is known to be a corepressor of Hairy-related proteins. TLE1 binds to AML1 through the Runt domain and the C terminus of AML1 that includes the VWRPY motif. The interaction is mainly mediated by the SP domain of TLE1. Moreover, TLE1 inhibits AML1-induced transactivation of the target promoters through the C terminus of AML1. These results suggest that TLE1 acts as a repressor of AML1 and provide important insights into the mechanism of the negative regulation of the AML1 functions in hematopoiesis and leukemogenesis.

Animals↗
PubMed1994

Effects of GABAA receptors activation on brain glucose metabolism in normal subjects and temporal lobe epilepsy (TLE) patients. A positron emission tomography (PET) study. Part I: Brain glucose metabolism is increased after GABAA receptors activation.

Though gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the human central nervous system, the metabolic response to GABA system activation remains imperfectly known. We studied in vivo with positron emission tomography (PET) the variations of glucose metabolism in the human brain after stimulation of the GABAA receptors by systemic administration of the specific GABAA agonist, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP). These investigations were performed in three normal volunteers and as part of presurgical evaluation for temporal lobe epilepsy in six patients. While clinical and electroencephalographic (EEG) monitoring showed a sedative effect and sleepiness after THIP administration, glucose metabolism was paradoxically increased in grey matter structures, which are known to have a high density of GABAA receptors. These findings suggest that the pharmacological activation of GABA pathways, although inhibitory and producing a decrease of vigilance, increases the energetic demand at least during a phase of GABA agonist action, probably at the synaptic or at the glial cell level.

Adult↗